A Phase Ib Study of GB491 Plus Letrozole in Patients With Advanced Breast Cancer
Study Details
Study Description
Brief Summary
GB491-005 is a multicenter, open-label, phase Ib Clinical Trial study to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD) activity, and preliminary anti-tumor activity of GB491 in combination with Letrozole in Previously Untreated Patients with HR-positive, HER2-negative Advanced Breast Cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GB491+Letrozole
|
Drug: GB491+Letrozole
Drug：The dose of GB491 is 150 mg, which should be taken with a meal and taken twice daily at approximately the same time each day, approximately 12 hours apart
|
Outcome Measures
Primary Outcome Measures
- DLT [During Cycle 1 (up to 28 days)]
Number of Participants with Dose-Limiting Toxicities for GB491 in Combination with Letrozole
- AE [From Baseline until 30 days after the last treatment]
Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)
Secondary Outcome Measures
- PFS [Approximately 2 years]
To assess the progression free survival assessed by investigator
- ORR [Approximately 2 years]
To assess the objective response rate for GB491 in Combination with Letrozole
- DOR [Approximately 2 years]
To assess the duration of response for GB491 in Combination with Letrozole
- DCR [Approximately 2 years]
To assess the disease control rate for GB491 in Combination with Letrozole
- CBR [Approximately 2 years]
To assess the clinical benefit rate for GB491 in Combination with Letrozole by investigator
- Plasma Concentration of GB491 [At predefined intervals from Cycle 1, Day 1 & Day 15; Cycle 2, Day 1 (each cycle is 28 days)]
Plasma Concentration of GB491 Over Time
- Plasma Concentration of Letrozole [At predefined intervals from Cycle 1, Day 1 & Day 15; Cycle 2, Day 1 (each cycle is 28 days)]
Plasma Concentration of Letrozole Over Time
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Females of 18 years of age or older at study screening
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Histologically or cytologically confirmed locally advanced or advanced metastatic breast cancer that is not amenable to curative surgical resection or radiation therapy
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The subject has been diagnosed with ER-positive breast cancer in the local laboratory
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The subject has HER2-negative breast cancer in the local laboratory
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Menopausal status is not limited (including Premenopausal/perimenopausal/postmenopausal state)
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No previous systemic anti-tumor treatment for locally advanced or metastatic breast cancer;
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According to RECIST V1.1, the patient has at least one measurable lesion that has not been irradiated by radiotherapy and can be evaluated by CT/MRI; If only bone metastases are present, there must be at least one osteolytic bone lesion that can be evaluated by CT/MRI
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ECOG performance status of 0 or 1
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Adequate organ and marrow function.
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The subject of childbearing potential must use one highly effective birth control method from the total duration of the study and 6 months after the last dose of study intervention.
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Provide informed consent
Exclusion Criteria:
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Previous treatment with CDK4/6 inhibitors
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Subjects with known hypersensitivity to any component of GB491 or Letrozole
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Patients with disease progression or recurrence during or within 1 year after completion of previous endocrine neoadjuvant or adjuvant therapy
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Known active, uncontrolled, or symptomatic central nervous system metastasis, carcinomatous meningitis, or clinically manifested leptomeningeal disease, cerebral edema, spinal compression or/and tumor progressive growth
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Visceral crisis
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Patients with skin lesion only and radiographically non-measurable at baseline
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Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia
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Major surgical procedure within 4 weeks of the first dose of study treatment or an anticipated need for major surgery, chemotherapy, radiotherapy, any other investigational drug or other anti-cancer therapy during the study
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Patients who have been on bisphosphonates and denosumab therapy at a stable dose for less than 14 days prior to randomization
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Patients who have received limited field radiotherapy in 2 weeks or extended field radiotherapy in 4 weeks before randomization or radiation with more than 30% of the bone marrow
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Subjects use drugs or fruits containing strong inducers or inhibitors of CYP3A4/5, or drugs with narrow therapeutic window that are mainly metabolized by CYP3A4/5 in 14 days before randomization
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Patients with long-term systematic use of corticosteroids
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Any severe and/or uncontrollable medical conditions
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Patients with severely impaired lung function
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Known history of HIV infection or history of HIV seropositivity
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Resting QTcF > 480 msec or there is a medical history of QTcF prolongation
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Subjects have significant hepatic disease
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Coagulation abnormalities
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Refractory nausea and vomiting, inability to swallow the formulated product, or other disease or clinical status would preclude adequate absorption, distribution, metabolism, or excretion of GB491
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Previous allogeneic bone marrow transplant
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Inflammatory breast cancer;
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Subjects with a history of other primary malignancies, except for non-melanoma skin cancer and cervical cancer in situ disease-free status ≥ 3 years
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Lactating women
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Unlikely to comply with study procedures, restrictions, and requirements
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Judgment by the investigator that the patient should not participate into the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China | 200032 |
Sponsors and Collaborators
- Genor Biopharma Co., Ltd.
Investigators
- Principal Investigator: Xichun Hu, PhD, Fudan University
- Principal Investigator: Jian Zhang, PhD, Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GB491-005